miRNA-711 Binds and Activates TRPA1 Extracellularly to Evoke Acute and Chronic Pruritus

Publication date: Available online 19 July 2018Source: NeuronAuthor(s): Qingjian Han, Di Liu, Marino Convertino, Zilong Wang, Changyu Jiang, Yong Ho Kim, Xin Luo, Xin Zhang, Andrea Nackley, Nikolay V. Dokholyan, Ru-Rong JiSummaryIncreasing evidence suggests that extracellular miRNAs may serve as biomarkers of diseases, but the physiological relevance of extracellular miRNA is unclear. We find that intradermal cheek injection of miR-711 induces TRPA1-depedent itch (scratching) without pain (wiping) in naive mice. Extracellular perfusion of miR-711 induces TRPA1 currents in both Trpa1-expressing heterologous cells and native sensory neurons through the core sequence GGGACCC. Computer simulations reveal that the core sequence binds several residues at the extracellular S5-S6 loop of TRPA1, which are critical for TRPA1 activation by miR-711 but not allyl isothiocyanate. Intradermal inoculation of human Myla cells induces lymphoma and chronic itch in immune-deficient mice, associated with increased serum levels of miR-711, secreted from cancer cells. Lymphoma-induced chronic itch is suppressed by miR-711 inhibitor and a blocking peptide that disrupts the miR-711/TRPA1 interaction. Our findings demonstrated an unconventional physiological role of extracellular naked miRNAs as itch mediators and ion channel modulators.
Source: Neuron - Category: Neuroscience Source Type: research